A new study from the US has shed new light on how a hallmark Alzheimer’s protein may cause brain cells to die. The study, which also tested the effects of the leukaemia drug Nilotinib in mice with features of Alzheimer’s, was published on Friday 31 October in the journal Molecular Neurodegeneration.
The researchers, led by a team at Georgetown University in Washington DC, set out to examine the interaction between two proteins that are involved in Alzheimer’s disease, amyloid and tau. Both proteins are present in the brain normally, but in Alzheimer’s, both begin to accumulate and become toxic to cells. The build-up of amyloid, which forms sticky clumps around nerve cells, is one of the first changes seen in the brain in Alzheimer’s and is thought by many scientists to be a ‘trigger’ for the disease process. However recent research has also focused on tau as a possible culprit. In a healthy brain, tau has an important function, acting as a form of ‘scaffolding’ to keeps cells stable, but in Alzheimer’s, tau loses its normal form and breaks away from the cell.
To investigate this, the team used cells in a dish to test how they responded to amyloid with and without tau. As part of the experiments, they used the cancer drug Nilotinib – which is used to treat leukaemia – to clear toxic amyloid from the cells. They found that when normal tau was present, the cells were better able to clear amyloid, suggesting that when tau is functioning properly, it plays a role in removing amyloid as it accumulates.
Further research in mice showed that injections of Nilotinib also cleared more amyloid when the mice had normally functioning tau. The researchers suggest that tau is crucial for cells to be able to clear the toxic amyloid protein properly, and that the build-up of tau is a key cause of nerve cell death.
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, the UK’s leading dementia research charity, said:
“Understanding why nerve cells die in Alzheimer’s is a key goal in the search for treatments, and this study adds to a body of evidence pointing to the tau protein as an important part of this process. Increasing evidence suggests abnormal tau and amyloid work together to cause nerve cell death, and this latest research provides new information to help scientists piece together a picture of what’s happening in Alzheimer’s. Although this study looked at the effects of Nilotinib in mice, these results are a long way from showing that the drug could help fight Alzheimer’s in people.
“Alzheimer’s is a complex disease with many different biological processes at play, and investment in research is vital to help scientists unpick the disease and understand how to fight it. With over half a million people living with Alzheimer’s in the UK, we urgently need better treatments capable of stopping the disease in its tracks.”